tbuckley/cabot-search huggingface dataset:
MagnetisMM-9: An open-label, multicenter, non-randomized phase 1/2 study of elranatamab in patients with relapsed/refractory multiple myeloma.
Authors: Rafael Fonseca, Junya Kuroda, Tadao Ishida, Rakesh Popat, Jeffrey S.Y. Huang, Anne Yver, Erik Vandendries, Mohamed Elmeliegy, Wei Dong Ma, Douglas W. Sborov
Journal: Journal of Clinical Oncology (2022)

TPS8068 Background: Elranatamab (PF-06863135) is a humanized bispecific antibody that targets both B cell maturation antigen (BCMA) on multiple myeloma (MM) cells and CD3 on T cells resulting in T cell- mediated cytotoxicity. In preclinical studies, elranatamab has demonstrated anti-myeloma activity and delayed disease progression. In the ongoing phase 1 MagnetisMM-1 study, elranatamab has demonstrated clinical efficacy and a manageable safety profile in patients with relapsed/refractory MM (Bahlis et al, J Clin Oncol 2021). Elranatamab maximum tolerated dose has not yet been reached. Subcutaneous (SC) elranatamab at the recommended dose of 76 mg QW on a 28-d cycle with a 2 step-up priming dose regimen administered during the first week is currently being evaluated in a phase 2 study, MagnetisMM-3 (Lesokhin et al, Blood, 2021). Methods: MagnetisMM-9 (start date: Oct 2021; estimated completion date: Apr 2025) is an open-label, multicenter, non-randomized phase 1/2 study evaluating an alternative priming regimen to further mitigate cytokine release syndrome (CRS) incidence and severity and to evaluate SC elranatamab Q2W and Q4W dosing regimens in patients with relapsed/refractory MM. In part 1 of the study, patients will receive premedications and 2 step-up priming doses on cycle 1 D1 (4 mg) and D4 (20 mg), followed by elranatamab 76 mg QW for 6 cycles, and a dose Q2W thereafter if partial response or better is achieved and maintained. In part 2, higher doses of elranatamab ( &gt; 76 mg) at increased intervals between doses will be evaluated. The primary endpoint is grade ≥2 CRS rate during cycle 1. Secondary endpoints include dose-limiting toxicities (part 2 only), objective response rate, duration of response, progression-free survival, overall survival, minimal residual disease negativity rate, safety, and pharmacokinetics. Eligible patients should be ≥18 years of age with a MM diagnosis and measurable disease according to IMWG criteria, refractory to at least one proteasome inhibitor, one immunomodulatory drug, and one anti-CD38 antibody, relapsed/refractory to their last treatment regimen, and have an ECOG performance status ≤1. Key exclusion criteria are smoldering MM, active plasma cell leukemia, amyloidosis, POEMS syndrome, stem cell transplant within 12 weeks of enrollment, active, uncontrolled bacterial, fungal, or viral infections, or any other active malignancy within 3 years prior to enrollment (except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ), or previous treatment with an anti-BCMA bispecific antibody. The study is open at centers in the USA, UK, Japan, and Taiwan. Clinical trial information: NCT05014412.
Correlation of psychological distress with quality of life and efficacy of immune checkpoint inhibitors in patients with newly diagnosed stage IIIB-IV NSCLC.
Authors: Fang Wu, Chunhong Hu, Yizheng Li, Yue Zeng, Junqi Liu, Xiaohan Liu, Fang Ma, Zhenhua Qiu, Chao Deng
Journal: Journal of Clinical Oncology (2022)

12001 Background: Psychological distress is common among cancer patients and leads to activation of the hypothalamic-pituitary-adrenal (HPA) axis and sympathetic nervous system (SNS) and continuous production of distress hormones, which may contribute to a highly immunosuppressive tumor microenvironment (TME). Meanwhile, preclinical studies have shown that psychological distress could undermine cancer therapies. Therefore, we investigate the prevalence of psychological distress in non-small-cell lung cancer (NSCLC) patients, identify its impact on quality of life (QoL) and efficacy of immune checkpoint inhibitors (ICIs), and explore the possible neuro-endocrinological mechanisms. Methods: Patients with newly diagnosed stage ⅢB-Ⅳ NSCLC received ICIs as first-line treatment were included. The assessments of psychological distress including depression and anxiety symptoms were measured using the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7), respectively. The QoL was measured by Short Form Health Survey 36 (SF-36). Stress hormones including serum cortisol, adrenocorticotropic hormone (ACTH), plasma epinephrine (Epi), and norepinephrine (NE) were determined by ELISA kit before treatment. Objective response rates (ORR) and Median progression-free (PFS) were estimated using the Chi-square test, Kaplan-Meier, and Cox regression method. Results: 77 NSCLC patients with a mean age of 60.9 years were enrolled. Stage distribution included 50 (64.9%) stage ⅢB/C and 27 (35.1%) stage Ⅳ. 44(57.1%) patients were present psychological distress. Psychological distress was associated with poorer QoL (P&lt;0.001). The median follow-up time was 16.2 months. Compared with non-psychological distress patients, psychological distress patients had a significant lower ORR (35.9% vs 63.64%; P=0.033) and shorter PFS (median 12.63 vs 14.60 months; 95% CI: 0.36 to 1.98; P=0.026). Moreover, psychological distress was the only independent predictor for PFS (HR:2.71, 95%CI: 1.06～6.90; P=0.037) in multivariate Cox regression analyses. The patients with psychological distress had higher levels of serum cortisol ( P=0.040) and plasma Epi ( P=0.023). Additionally, the serum cortisol ( P=0.043) and plasma Epi ( P=0.025) concentrations were associated with inferior ICIs response. Conclusions: Psychological distress is common within stage ⅢB-Ⅳ NSCLC patients. Patients with psychological distress are associated with worse QoL and inferior outcomes to ICIs and discover the potential mechanisms of neuro-endocrinological hormones in resistance to ICIs therapy.
Comprehensive analysis of FGFR mutations in Chinese cancer patients.
Authors: Tao Yu, Zhichao Fu
Journal: Journal of Clinical Oncology (2022)

e15117 Background: Fibroblast growth factor receptors (FGFRs) are highly conserved transmembrane tyrosine kinase receptors (RTKS) that regulating several cellular processes such as proliferation, differentiation, migration and survival. In recent years, some studies have documented that signaling through FGFRs impact progression of cancer and the survival of patients with cancer. As a potential therapeutic target, exploring the mutation frequency of FGFRs in more different cancers are necessary. Here we performed a comprehensive analysis of the frequency and types of FGFRs mutations in Chinese cancer patients and provided reference for targeted therapy development. Methods: From January 2020 to December 2021, a total of 4,102 patients with nine common cancers were included in the study. The next-generation sequencing was utilized for detecting genetic mutations. Results: A total 328 patients (7.9%) with FGFR mutation were identified. The FGFR 3 was the most frequently gene in our cohort. Among all the cancer patients, the highest frequency of FGFR mutations was observed in bladder cancer (32.5%) and the percentages in FGFR1, FGFR2 and, FGFR3 were 2.7%, 1.35%, and 6.76% respectively. Furthermore, the proportion of FGFR mutation in lung carcinoma, cholangiocarcinoma, colorectal carcinoma, melanoma, breast carcinoma and ovarian carcinoma was 8.64%, 11.58%, 13%, 16.7%, 9.62% and 10.81% respectively. Additionally, FGFR mutation have been detected in other tumor types, including renal cell carcinoma (5.63%), prostate cancer (5.45%), and gastric carcinoma (13.72%). Conclusions: The present study provided the comprehensive FGFR mutation data of Chinese cancer patients. A high frequency mutation in FGFR have been found in Chinese patients with different cancers, which mean that patients with multiple cancer types might benefit from development of efficient EGFR inhibitors.
More than just “vaginal dryness”: Addressing an unmet need for sexual health intervention in female cancer survivors.
Authors: Fay Pon, Sanjana Satish, Frank J. Penedo, Kristin E. Rojas
Journal: Journal of Clinical Oncology (2022)

e24050 Background: Female sexual dysfunction (FSD) in cancer survivors is underreported and therefore undertreated. This study aims to describe the population of female cancer survivors seeking treatment for sexual dysfunction through a novel sexual health after cancer program. Methods: We conducted a retrospective analysis to characterize patients presenting to the MUSIC (Menopause, Urogenital, Sexual Health and Intimacy Clinic) Program at a NCI-designated cancer center in South Florida. Patients received a baseline Female Sexual Function Index (FSFI) and underwent a physical, including abdominopelvic, exam. The FSFI is a 19-item survey previously validated for use in female cancer survivors. Severity of dysfunction (by presenting symptom, physical exam, and FSFI) was correlated to demographic and cancer characteristics. Sexual dysfunction was defined as ≤26.55. Results: Between 2020-2021, 104 female cis-gender women with a median age of 46 (range 19-75) at diagnosis were seen. 56% identified as Hispanic/Latinx. Most were treated for breast (80%) or gynecologic (10%) cancer. Common presenting symptoms included vaginal dryness (55%), painful sex (45%), low desire (36%) and hot flashes (22%). Patients who disclosed details about pain (n = 62) reported penetration was possible but uncomfortable (16%), possible but painful (66%) or impossible due to pain (18%). Those who disclosed changes with orgasm (n = 43) reported it was more difficult (26%), or impossible (23%). Of those completing the FSFI (n = 66), median Desire Domain score was 1.2 (IQR 1.2-2.4), and median Total Score was 8.1 (IQR 2.9-16.4), with 97% of patients meeting criteria for FSD (Table). Conclusions: The present study highlights a continued unmet need to address severe sexual health concerns in the growing female cancer survivor population. Future work will describe treatment strategies employed and their effectiveness at symptom resolution and quality-of-life improvement.[Table: see text]
A phase I study of anlotinib with concurrent chemoradiotherapy for limited-stage small cell lung cancer.
Authors: Dingzhi Huang, Kai Ren, Xinyue Wang, Li Lin, Jinliang Chen, Liuchun Wang, Zhaoting Meng, Lujun Zhao
Journal: Journal of Clinical Oncology (2022)

8579 Background: Concurrent chemoradiotherapy (CCRT) is the standard treatment for limited-stage small-cell lung cancer (LS-SCLC). However, LS-SCLC remains an area of high unmet medical need. Anlotinib is an antiangiogenic multi-target tyrosine kinase inhibitor. In the phase II ALTER-1202 trial, anlotinib significantly improved clinical outcomes in advanced small-cell lung cancer. We report here a phase 1 trial of anlotinib with CCRT for LS-SCLC. Methods: This is a prospective, single-arm, phase I clinical trial using a 3+3 design. Patients aged between 18 and 75 with previously untreated LS-SCLC, PS 0-1 and adequate organ function are eligible. Patients received anlotinib (12mg, qd, d1-14, q3w) and chemotherapy (etoposide, 100 mg/m 2 , d1-3, q3w and cisplatin, 25 mg/m 2 , d1-3, q3w) for cycle 1, then anlotinib [dose escalation at 3 levels (DL1-3) 8mg, 10mg and 12mg, qd, d1-14, q3w], chemotherapy (etoposide, 50 mg/m 2 , d1-5, q4w and cisplatin, 25 mg/m 2 , d1-3, q4w) and thoracic radiotherapy (60-66 Gy in 30-33 daily 2-Gy fractions starting on day 1 of cycle 2) for cycles 2–3, then anlotinib (12mg, qd, d1-14, q3w) and chemotherapy (etoposide, 100 mg/m2, d1-3, q3w and cisplatin, 25 mg/m 2 , d1-3, q3w) for cycles 4-6. Cycles 5-6 were given as appropriate according to the patient's physical condition. Prophylactic cranial radiation was given according to the judgment of the investigator after CCRT. The purpose of this study is to determine the maximum tolerated dose (MTD) of anlotinib when combination with CCRT. Results: Twelve patients were enrolled from May 2020 to September 2021. No DLTs were observed in DL1 (3 patients) or DL2 (3 patients). At DL3 (6 patients), 1 patient had a DLT of grade 3 pulmonary embolism. Grade 3 adverse events were white blood cell count decreased, neutrophil count decreased, lymphocyte count decreased, hypertension, albumin decreased and pulmonary embolism. One patient had grade 3 pulmonary embolism and grade 4 neutrophil count decreased in DL3 at cycle 1. One patient had grade 2 radiation pneumonitis after cycle 5 and grade 1 radiation esophagitis at cycle 3 in DL3. One patient had grade 2 radiation esophagitis at cycle 3 in DL2. The MTD was not reached. Conclusions: Combined treatment with anlotinib and CCRT for limited-stage small cell lung cancer is well tolerated and further clinical investigation is warranted. Clinical trial information: NCT04882033.
Phase I dose-escalation study of IBI351 (GFH925) monotherapy in patients with advanced solid tumors.
Authors: Qing Zhou, Nong Yang, Jun Zhao, Xiaorong Dong, Huijuan Wang, Ying Yuan, Yan Yu, Meijiang Zhang, Sujie Zhang, Mengna Huang, Yuping Shen, Yi-Long Wu
Journal: Journal of Clinical Oncology (2022)

3110 Background: IBI351(GFH925) is an irreversibly covalent inhibitor of KRAS G12C . In this first-in-human dose-escalation study, we report the preliminary safety and anti-tumor activity of IBI351 (GFH925) in patients (pts) with advanced solid tumors harboring the KRAS p.G12C mutation. Methods: Pts with locally advanced, recurrent or metastatic solid tumors with KRAS G12C mutation for whom standard therapy had failed were enrolled. Phase I dose escalation had an accelerated titration design for dose level 250mg QD and a BOIN design with 450/700/900mg QD. The primary end points were safety and tolerabilityThe secondary end points were pharmacokinetics (PK) and anti-tumor activity of IBI351(GFH925) monotherapy per RECIST v1.1. Results: As of Feb 07 2022, 15 pts (13 men, 2 women; median age: 62 yrs, range: 48–74 yrs) were enrolled, among whom 12 had non-small cell lung cancer (NSCLC), and 3 had colorectal cancer (CRC). 4 pts had ≥3 prior lines of treatment (tx). Median tx duration was 66.5 ds (range: 21–98 ds). No dose-limiting toxicity (DLT) or any ≥grade 3 treatment-related adverse events were observed in any dose cohorts. A total of 12 patients (80.0%) had treatment-related adverse events (grade 1, n = 6; grade 2, n = 6). By investigator-assessment, tumor response was evaluated in 9 pts (4 with ≥2 assessments); 6 pts had not reached their first assessment. 2 pts had PR (1 NSCLC at wks 12, 450mg, tx ongoing; 1 CRC at wks 6, 700mg, tx ongoing), 4 pts (NSCLC) had SD, and 3 pts had PD (1 NSCLC at wks 12, 2 CRC at wks 6). As data cut-off date, 11 pts were continuing to receive IBI351 (GFH925). Conclusions: IBI351(GFH925) was well-tolerated without unanticipated adverse events across all doses explored in pts with advanced solid tumors harboring the KRAS p.G12C mutation. The data also demonstrated the preliminary efficacy signal of IBI351 (GFH925) in previously treated advanced NSCLC and CRC. Clinical trial information: NCT05005234.
Increasing advance directive completion within the 4R oncology model in breast cancer patients prior to surgery in a racially diverse patient population.
Authors: Stephanie Ossowski, Liisa Lyon, Elizabeth Shurell Linehan, Nancy P. Gordon, Olga Egorova, Becky Mark, Kimberly Beringer, Thea Abbe, Aida Shirazi, Christine B. Weldon, Julia R. Trosman, Arliene Ravelo Mangalindan, Raymond Liu
Journal: Journal of Clinical Oncology (2022)

e13511 Background: Advance directives (ADs) are an important part of life care planning in patients with cancer. There is a lack of effective interventions that increase AD rates in breast cancer patients prior to surgery. In this quality improvement project, we implemented a 4R Oncology intervention in a community-based cancer center within an integrated health care system. 4R (Right Info / Care / Patient / Time) is a novel care planning and delivery model, which enables patients and care teams to manage complex time-sensitive care with a multi-modality 4R Care Sequence plan, coupled with follow-up workflows. Methods: Patients with newly diagnosed non-metastatic breast cancer who attended a multidisciplinary clinic and underwent definitive surgery at one facility were included in the study. Patients received usual care from 10/1/19 to 9/30/20 (usual care cohort). From 10/1/20 to 9/30/21 (intervention cohort), patients were provided a 4R Care Sequence, which included AD completion prior to surgery, and those without AD were referred for follow-up with a health educator to discuss AD completion. Demographics, NCCN thermometer distress scores, and AD completion rates were compared between the usual care and intervention cohorts using descriptive statistics. Results: Characteristics of age, gender, race/ethnicity, language interpreter usage, Elixhauser Comorbidity Index, NCCN distress scores &gt; 4, surgery type, tumor grade, ER/PR/HER-2 status were similar between the usual care (N=140) and intervention cohorts (N=141). The intervention improved AD completion rates in a time-sensitive fashion prior to surgery between usual care and intervention cohorts, both in total (15% vs 74%, p&lt;.01), and in 3 of the 5 race/ethnicity groups (Table). AD completion rates increased in patients of all races/ethnicities, but increases were not statistically significant for Hispanic patients, likely due to low numbers of these patients in both cohorts. Patients with higher distress scores completed ADs at similar rates to those with lower distress scores. Conclusions: Delivery of 4R Care Sequences, coupled with a health educator follow-up can significantly increase rates of time-sensitive AD completion, regardless of patients’ distress score. Patients across race/ethnicity groups benefited from the intervention, but further efforts are needed to understand the impact of this intervention in patients who are Hispanic. Through an effective care delivery model, patients can be provided with standardized equitable care. [Table: see text]
14-gene immunoglobulin (IGG) and proliferation signatures and association with overall survival across cancer-types.
Authors: Francesco Schettini, Laia Paré, Mercedes Marín-Aguilera, Susana Puig, Laura Mezquita, Neus Baste, Tomás Pascual, Olga Martinez Saez, Benedetta Conte, Pedro Jares, Joan Anton Puig-Butillé, Esther Sanfeliu Torres, Blanca González-Farre, Patricia Villagrasa, Pier Franco Conte, Charles Perou, Joel S. Parker, Fara Brasó Maristany, Aleix Prat
Journal: Journal of Clinical Oncology (2022)

2636 Background: The HER2DX prognostic assay in early-stage HER2-positive breast cancer integrates clinical variables and 4 gene expression signatures (GES) tracking IGG, tumor proliferation, luminal cell differentiation, and the expression of the HER2 amplicon. Here, we assessed the prognostic value across cancer-types of each of these four individual GES and a research-based version of the HER2DX risk-score. Methods: RSEM batch normalized RNA-sequencing gene expression data from The Cancer Genome Atlas (TCGA) project were downloaded from cBioPortal. The association between a research-based version of the HER2DX risk-score, and each GES, with overall survival (OS) was assessed as continuous variables using univariate Cox regression model. The research-based version of the HER2DX risk-score tested did not include clinical variables. The Cox model was applied to estimate hazard ratios (HR) with 95% confidence intervals. The threshold for statistical significance was set at p&lt; 0.05. Results: Gene expression data from 9,852 patients representing 30 different cancer-types were evaluated. The proliferation, IGG, luminal and HER2 amplicon GES were significantly associated with OS in 40.0%, 33.3%, 23.0% and 6.7% of the cancer-types tested, respectively. The IGG GES was found significantly associated with a favorable OS in breast cancer (HR: 0.73, p &lt; 0.001), cervical and head &amp; neck squamous cell carcinomas (HR: 0.75, p = 0.021 and HR: 0.78, p &lt; 0.001), lung adenocarcinoma (HR: 0.84, p = 0.020), skin melanoma (HR: 0.73, p &lt; 0.001) and sarcomas (HR: 0.78, p = 0.029). Conversely, association of IGG GES with unfavorable OS was observed in uveal melanoma (HR: 1.74, p = 0.008), kidney clear cell and papillary cell carcinomas (HR: 1.29, p &lt; 0.001 and HR: 1.44, p = 0.017, respectively), as well as brain low-grade gliomas (LGG) (HR: 1.56, p &lt; 0.001). Finally, the research-based HER2DX risk-score was found significantly associated with OS in 11 of 30 (36.7%) cancer-types, including breast (HR: 1.42, p &lt; 0.001) cervical and head &amp; neck squamous cells cancers (HR: 1.36, p = 0.018 and HR: 1.30, p &lt; 0.001), lung adenocarcinoma (HR: 1.34, p &lt; 0.001), skin melanoma (HR: 1.34, p &lt; 0.001), sarcomas (HR: 1.41, p = 0.003), adrenocortical carcinoma (HR: 2.31, p &lt; 0.001), endometrial carcinoma (HR: 1.36, p = 0.005), hepatocarcinoma (HR: 1.26, p = 0.012), LGG (HR: 1.37, p = 0.001) and mesothelioma (HR: 1.48, p = 0.005). Conclusions: The 14-gene IGG and proliferation signatures are strong prognostic biomarkers across cancer-types. The opposite association of IGG with OS depending on the cancer-type warrants further investigation.
A phase 1b/2 study of batiraxcept (AVB-S6-500) in combination with cabozantinib in patients with advanced or metastatic clear cell renal cell (ccRCC) carcinoma who have received front-line treatment (NCT04300140).
Authors: Neil J. Shah, Katy Beckermann, Nicholas J. Vogelzang, Shifeng S. Mao, Moshe Chaim Ornstein, Hans J. Hammers, Xin Gao, David F. McDermott, Naomi B. Haas, Hongxia Yan, Vanessa Esquibel, Reshma A. Rangwala, Matthew T Campbell
Journal: Journal of Clinical Oncology (2022)

4511 Background: AXL is up-regulated by hypoxia-inducible factor-1 signaling in both VHL-deficient and hypoxic tumor cells and plays a critical role in the metastatic phenotype of ccRCC. Batiraxcept is a recombinant fusion protein containing an extracellular region of human AXL combined with the human immunoglobulin G1 heavy chain (Fc), demonstrating highly potent, specific AXL inhibition. Methods: Batiraxcept at doses of 15 and 20 mg/kg, plus cabozantinib 60 mg daily, was evaluated using a 3+3 dose escalation study design. The primary objective was safety; secondary and exploratory objectives included identification of the recommended phase 2 dose (RP2D), overall response rate (ORR), and duration of response (DOR). Correlation of serum soluble AXL (sAXL)/GAS6 with ORR was evaluated. Key eligibility criteria include previously treated (2L+) ccRCC patients; prior treatment with cabozantanib was not allowed. sAXL/GAS6 was evaluated at baseline. Results: Data as of 4-February-2022, Phase 1b enrolled 26 patients, 16 patients treated with 15 mg/kg and 10 patients with 20 mg/kg dose of batiraxcept. Baseline characteristics: median age 60 (40-81); male 22 (85%); median prior line of therapy 1 (1-5); IMDC risk group of favorable 6 (23%); prior VEGF inhibitor 15 (58%); 100% with prior immunotherapy. At median follow up of 4.9 months, 92% (n=24) patients remained on the study. No dose limiting toxicities were observed at either 15 mg/kg or 20 mg/kg dose. Batiraxcept and cabozantinib related adverse events (AEs) occurred in 17 subjects (65%). Most common related AE include decreased appetite 31% (n=8), diarrhea and fatigue 23% (n=6). Grade 3 related AEs occurred in 4 patients (15%) including diarrhea, thromboembolism, hypertension, small bowel obstruction, and thrombocytopenia (n=1, 4% each) being most common. No grade 4 or 5 related AEs were observed. The ORR was 46% (n=12, partial response [PR]; Table). No patients had primary progressive disease. Among the patients who had baseline sAXL/GAS6 ratio of ≥ 2.3, the ORR was 67% (12/18). Regardless of baseline sAXL/GAS6 ratio, 3-month DOR was 100%; and 6-month progression free survival was 79%. Batiraxcept PK levels were similar across both doses and GAS6 levels suppressed through the dosing period. Conclusions: Batiraxcept plus cabozantinib is well tolerated. The RP2D of batiraxcept was identified as 15 mg/kg. Early efficacy signals were observed including 100% DOR at 3 months. Baseline sAXL/GAS6 may serve as a potential biomarker to enrich the population. Clinical trial information: NCT04300140. [Table: see text]